This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → Aromatic Compounds Degradation → Nicotinate Degradation|
Some taxa known to possess this pathway include : Eubacterium barkeri
Expected Taxonomic Range: Firmicutes
Nicotinate (niacin, vitamin B3, 3-pyridinecarboxylate) is a pyridine ring-containing compound. Microorganisms have multiple ways of degrading pyridine and its derivatives, and degradation of these compounds is relevant to both biological and industrial processes. The degradation of nicotinate by both aerobic and anaerobic organisms involves the initial formation of 6-hydroxynicotinate, but the pathways diverge after that. Among aerobic organisms, the pathways in Pseudomonas and Bacillus niacini are shown in MetaCyc pathways nicotinate degradation I, and nicotinate degradation II, respectively. An anaerobic pathway for nicotinate degradation in Eubacterium barkeri (previously knowns as Clostridium barkeri) is shown here ( [Stadtman72] and reviewed in [Kaiser96, Berry87, Eggerer85]). This anaerobic fermentation pathway results in the formation of equimolar amounts of propionate, acetate, carbon dioxide and ammonia [Stadtman72]. The acetate and carbon dioxide are thought to be derived from pyruvate [Kung71a], as indicated by the pathway link.
The first reaction is ring hydroxylation, resulting in the formation of 6-hydroxynicotinate (sometimes shown in its 6-oxo tautomeric form) [Berry87, Stadtman72]. The next reaction is ring reduction. The following three reactions have been elucidated by the discovery of two chiral intermediates and three enzymes [Alhapel06]. These investigators also cloned the entire gene cluster encoding the nicotinate fermentation enzymes in Eubacterium barkeri. The enamidase is a bifunctional hydrolase that produces the chiral 2-formylglutarate and ammonia. This compound is then reduced to the chiral (S)-2-hydroxymethylglutarate. The next reaction is probably catalyzed by the product of gene hmd, predicted to be 2-(hydroxymethyl)glutarate dehydratase based on amino acid sequence similarity to bacterial [4Fe-4S]-containing serine dehydratases [Alhapel06]. A vitamin B12 coenzyme-dependent mutase catalyzes a key rearrangement to form 2-methylene-3-methylsuccinate (methylitaconate). A reaction involving double bond migration results in the formation of dimethylmaleate. Hydration and cleavage reactions produce propionate and pyruvate. There is evidence that degradation of pyruvate via a ferredoxin-linked process, with acetyl-CoA and acetyl phosphate intermediates, results in ATP generation and the formation of acetate and carbon dioxide [Kung71a, KollmannKoch84]. Reviewed in [Kaiser96, Eggerer85].
Superpathways: superpathway of nicotinate degradation
Alhapel06: Alhapel A, Darley DJ, Wagener N, Eckel E, Elsner N, Pierik AJ (2006). "Molecular and functional analysis of nicotinate catabolism in Eubacterium barkeri." Proc Natl Acad Sci U S A 103(33);12341-6. PMID: 16894175
Kaiser96: Kaiser JP, Feng Y, Bollag JM (1996). "Microbial metabolism of pyridine, quinoline, acridine, and their derivatives under aerobic and anaerobic conditions." Microbiol Rev 60(3);483-98. PMID: 8840783
Kung71a: Kung H, Tsai L, Stadtman TC (1971). "Nicotinic acid metabolism. 8. Tracer studies on the intermediary roles of -methyleneglutarate, methylitaconate, dimethylmaleate, and pyruvate." J Biol Chem 246(21);6444-51. PMID: 4332128
Beatrix94: Beatrix B, Zelder O, Linder D, Buckel W (1994). "Cloning, sequencing and expression of the gene encoding the coenzyme B12-dependent 2-methyleneglutarate mutase from Clostridium barkeri in Escherichia coli." Eur J Biochem 221(1);101-9. PMID: 8168499
Gladyshev94: Gladyshev VN, Khangulov SV, Stadtman TC (1994). "Nicotinic acid hydroxylase from Clostridium barkeri: electron paramagnetic resonance studies show that selenium is coordinated with molybdenum in the catalytically active selenium-dependent enzyme." Proc Natl Acad Sci U S A 91(1);232-6. PMID: 8278371
Gladyshev96: Gladyshev VN, Khangulov SV, Stadtman TC (1996). "Properties of the selenium- and molybdenum-containing nicotinic acid hydroxylase from Clostridium barkeri." Biochemistry 35(1);212-23. PMID: 8555176
Holcenberg69a: Holcenberg JS, Tsai L (1969). "Nicotinic acid metabolism. IV. Ferredoxin-dependent reduction of 6-hydroxynicotinic acid to 6-oxo-1,4,5,6-tetrahydronicotinic acid." J Biol Chem 244(5);1204-11. PMID: 5767303
Kung71: Kung HF, Stadtman TC (1971). "Nicotinic acid metabolism. VI. Purification and properties of alpha-methyleneglutarate mutase (B 12-dependent) and methylitaconate isomerase." J Biol Chem 246(10);3378-88. PMID: 5574401
Michel89: Michel C, Hartrampf G, Buckel W (1989). "Assay and purification of the adenosylcobalamin-dependent 2-methyleneglutarate mutase from Clostridium barkeri." Eur J Biochem 184(1);103-7. PMID: 2776761
Michel91: Michel C, Buckel W, Linder D (1991). "Purification of the coenzyme B12-containing 2-methyleneglutarate mutase from Clostridium barkeri by high-performance liquid chromatography." J Chromatogr 587(1);93-9. PMID: 1783665
Michel91a: Michel C, Buckel W (1991). "Coenzyme B12-dependent 2-methyleneglutarate mutase from Clostridium barkeri. Protection by the substrate from inactivation by light." FEBS Lett 281(1-2);108-10. PMID: 2015880
Park06: Park YJ, Yoo CB, Choi SY, Lee HB (2006). "Purifications and characterizations of a ferredoxin and its related 2-oxoacid:ferredoxin oxidoreductase from the hyperthermophilic archaeon, Sulfolobus solfataricus P1." J Biochem Mol Biol 39(1);46-54. PMID: 16466637
Pierik05: Pierik AJ, Ciceri D, Lopez RF, Kroll F, Broker G, Beatrix B, Buckel W, Golding BT (2005). "Searching for intermediates in the carbon skeleton rearrangement of 2-methyleneglutarate to (R)-3-methylitaconate catalyzed by coenzyme B12-dependent 2-methyleneglutarate mutase from Eubacterium barkeri." Biochemistry 44(31);10541-51. PMID: 16060663
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